BORC functions upstream of kinesins 1 and 3 to coordinate regional movement of lysosomes along different microtubule tracks
Open accessAbstract
The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A). Remarkably, KIF5B preferentially moves lysosomes on perinuclear tracks enriched in acetylated α-tubulin, whereas KIF1Bβ and KIF1A drive lysosome movement on more rectilinear, peripheral tracks enriched in tyrosinated α-tubulin. These findings establish BORC as a master regulator of lysosome positioning through coupling to different kinesins and microtubule tracks. Common regulation by BORC enables coordinate control of lysosome movement in different regions of the cell.
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The G234A rigor mutant of Kinesin-1 binds to and effectively decorates acetylated microtubules.
“Similar to the active motor, the G234A rigor mutant of Kinesin-1 binds to and effectively decorates acetylated MTs (Tas et al., 2017; Guardia et al., 2016; Farías et al., 2017).”
From A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle (2023) · cites this paper as Guardia et al., 2016
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Cites
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- Authors
- Guardia, C. M., Farías, G. G., Jia, R., Pu, J., & Bonifacino, J. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Bonifacino, Juan S.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 17
- Issue
- 8
- Pages
- 1950-1961
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5136296
- OpenAlex
- W2556134275
- Cited by
- 269
- References
- 4
- Citations by year
- 2026: 24 · 2025: 23 · 2024: 46 · 2023: 31 · 2022: 32 · 2021: 28 · 2020: 28 · 2019: 21 · 2018: 16 · 2017: 19 · 2016: 1
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NICHD
- NIH (ZIA HD001607)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- lysosome transport, kinesin-1, kinesin-3, KIF5B, KIF1A, tubulin acetylation, tubulin tyrosination, dynein, lysosome positioning, bidirectional transport, small GTPases
- MeSH terms
- Biological Transport, Cell Membrane, Dyneins, HeLa Cells, Humans, Lysosomes, Microtubules, Models, Biological, Mutation, Kinesins, Multiprotein Complexes
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